title: Accelerated experience-dependent pruning of cortical synapses in ephrin-A2 knockout mice.
abstract: Refinement of mammalian neural circuits involves substantial experience-dependent synapse elimination. Using in vivo two-photon imaging, we found that experience-dependent elimination of postsynaptic dendritic spines in the cortex was accelerated in ephrin-A2 knockout (KO) mice, resulting in fewer adolescent spines integrated into adult circuits. Such increased spine removal in ephrin-A2 KOs depended on activation of glutamate receptors, as blockade of the N-methyl-D-aspartate (NMDA) receptors eliminated the difference in spine loss between wild-type and KO mice. We also showed that ephrin-A2 in the cortex colocalized with glial glutamate transporters, which were significantly downregulated in ephrin-A2 KOs. Consistently, glial glutamate transport was reduced in ephrin-A2 KOs, resulting in an accumulation of synaptic glutamate. Finally, inhibition of glial glutamate uptake promoted spine elimination in wild-type mice, resembling the phenotype of ephrin-A2 KOs. Together, our results suggest that ephrin-A2 regulates experience-dependent, NMDA receptor-mediated synaptic pruning through glial glutamate transport during maturation of the mouse cortex.
authors.affiliation: Department of Molecular Cell and Developmental Biology, University of California, Santa Cruz, Santa Cruz, CA 95064, USA.
authors.forename: Xinzhu
authors.initials: X
authors.lastname: Yu
authors.forename: Gordon
authors.initials: G
authors.lastname: Wang
authors.forename: Anthony
authors.initials: A
authors.lastname: Gilmore
authors.forename: Ada Xin
authors.initials: AX
authors.lastname: Yee
authors.forename: Xiang
authors.initials: X
authors.lastname: Li
authors.forename: Tonghui
authors.initials: T
authors.lastname: Xu
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Smith
authors.forename: Lu
authors.initials: L
authors.lastname: Chen
authors.forename: Yi
authors.initials: Y
authors.lastname: Zuo
mesh_terms: D027322:Amino Acid Transport System X-AG / Q000378:metabolism; D000818:Animals; D001921:Brain / Q000254:growth & development; D049229:Dendritic Spines / Q000378:metabolism; D036383:Ephrin-A2 / Q000172:deficiency / Q000235:genetics*; D019706:Excitatory Postsynaptic Potentials / Q000235:genetics; D051379:Mice; D018345:Mice, Knockout; D009457:Neuroglia / Q000378:metabolism*; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism; D013569:Synapses / Q000378:metabolism*; D009435:Synaptic Transmission / Q000502:physiology
chemical_list: D027322:Amino Acid Transport System X-AG; D036383:Ephrin-A2; D016194:Receptors, N-Methyl-D-Aspartate